Cancer and other diseases caused by the presence of unwanted cells create significant loss of life, suffering, and economic impact. Immunotherapeutic strategies for targeting cancer have been an active area of translational clinical research.
WO 2012/123755 discusses the concept of re-directed immunotherapy. In this application, an agent for preventing or treating a condition characterized by the presence of unwanted cells includes a targeting moiety that is capable of targeting to the unwanted cells and a T-cell epitope that can be released from the targeting moiety by selective cleavage of a cleavage site in the agent in the vicinity of the unwanted cells.
WO 2014/043523 teaches an agent based on an ScFV directed to cancer cells including from 1-10 immunogenic CD8 T-cell epitopes in one of the following two arrangements: T-c-En-c-Fcn or T-c-Fcn-c-En, where T is the ScFv, En is from 1-10 CD8 T-cell epitopes, c: is a protease cleavage site, and Fcn is from 1-10 Fc portions of an IgG antibody. In this reference, the 1-10 immunogenic CD8 T-cells are released from the ScFv and Fc portions of the agent in a single polypeptide chain, still conjugated to each other.
While some positive test data has been shown with prior approaches, clinically-effective therapeutic strategies must be able to elicit a strong immune response in an individual suffering from a disease such as cancer. Additionally, effective therapies should work well in a wide cross-section of patients from different racial and ethnic groups. Maximally-effective therapies would also generate an immune response against the unwanted cells without generating an inhibitory immune response against the therapeutic agent itself so that multiple rounds of treatment could be administered over a period of time. Therefore, additional developments in this field of re-directed immunotherapy are required.